2-OP, also chemically named 2-cyanopyridine, pyridine-2-carbonitrile and 2-pyridinecarbonitrile and with a CAS Number of 100-70-9, is a white to light brown needle-like crystal having a melting point of 24˜27° C. As an important intermediate, 2-OP has been widely used in the synthesis of various fine organic chemicals such as pharmaceuticals, agrochemicals and dyes, and most of these chemicals exhibit various excellent properties. For example, the new herbicide picloram prepared from the 2-OP has the advantages of high efficacy, good selectivity, low toxicity and small residual amount and short residual period in soil and plant, suitable for the control of the most dicotyledonous weeds and shrubs in the fields of wheat, corn and sorghum. Moreover, the 2-OP can also be used to synthesize 2-amino-5-chloropyridine which is an important intermediate in the manufacture of a novel oral anticoagulant betrixaban.
There are several methods of synthesizing the 2-OP, including catalytic 2-methylpyridine ammoxidation method, cyano substitution method, pyridine-2-carboxaldoxime method and 2-aminopyridine method. Regarding the catalytic 2-methylpyridine ammoxidation method, a mixture of nitrogen and oxygen is used as an oxidant to directly oxidize the 2-methylpyridine into the 2-OP at high temperature in the presence of a catalyst. In the cyano substitution method, 2-halopyridine is reacted with acetone cyanohydrin and an inorganic alkali metal cyanide under a certain condition to enable the substitution of the halogen atom with a cyano group to form the 2-OP. As for the pyridine-2-carboxaldoxime method, pyridine-2-carboxaldoxime is directly dehydrated in the presence of a dehydrating agent or hydrated at high temperature to give the 2-OP. In the 2-aminopyridine method, the 2-aminopyridine is diazotized to form a pyridine diazonium salt, which subsequently undergoes Sandmeyer reaction with cuprous cyanide to produce the 2-OP. The catalytic 2-methylpyridine ammoxidation method emerges from such methods and is widely used in actual production because of sufficient source, absence of highly-toxic cyanide, high safety and less cost.
There are two conversion pathways in the preparation of the 2-OP using the catalytic 2-methylpyridine ammoxidation in the presence of high temperature and a catalyst. In one pathway, 2-methylpyridine is oxidized into pyridine-2-carboxaldehyde in the presence of a catalyst, and then the pyridine-2-carboxaldehyde is reacted with ammonia to form pyridine-2-methylenimine which is dehydrogenated to produce the 2-OP. While in the other pathway, after 2-methylpyridine is oxidized into pyridine-2-carboxaldehyde in the presence of a catalyst, the pyridine-2-carboxaldehyde is continuously oxidized into pyridine-2-carboxylic acid, which is then reacted with ammonia at high temperature to form pyridine-2-carboxamide. The pyridine-2-carboxamide is subsequently dehydrated at high temperature to produce the 2-OP. Actually, in the process of preparing the 2-OP from 2-methylpyridine by catalytic ammoxidation, the oxidized product is generally required to be rectified to obtain the 2-OP with high purity, while a large amount of rectification residue is simultaneously generated, the amount of which is about 10%-15% of the 2-OP production. Currently, the residues formed in the rectification are treated as a hazardous solid waste, and are subjected to harmless treatment by high-temperature incineration and then landfilled or mineralized. However, such a treatment requires a large amount of energy and often fails to obtain the absolutely harmless rectification residues. In addition, some fine chemicals such as pyridine-2-carboxamide and pyridine-2-carboxaldehyde may exist in the rectification residues derived from the process of preparing the 2-OP from 2-methylpyridine by the catalytic ammoxidation, so the high-temperature incineration treatment may result in insufficient utilization of the residues.
Chromium(III) pyridine-2-carboxylate, also named pyridine-2-carboxylic acid chromium(III) salt, chromium(III) 2-pyridinecarboxylate, chromium(III) picolinate, tris (picolinate) chromium(III) and picolinic acid chromium(III) salt and with CAS Number of 14639-25-9, is a violet to purplish red crystalline powder, which can succeed in passing through the cell membrane and directly act on tissue cells, enhancing the activity of insulin and improving the glycometabolism.
Chromium(III) pyridine-2-carboxylate is chemically stable at room temperature, slightly soluble in water and insoluble in ethanol. Additionally, chromium(III) pyridine-2-carboxylate has electrically-neutral molecular structure and hydrophobicity, so that it can undergo the transmembrane absorption in a complete structure. The GTF (Glucose Tolerance Factor)-like structure of chromium(III) pyridine-2-carboxylate can facilitate its absorption and the exertion of its biological functions. Moreover, chromium(III) pyridine-2-carboxylate is a supplement which plays a role in strengthening muscles and losing weight, and it can also increase the amount of active AMP protein kinase (AMPK) involving in metabolic pathways in skeletal muscle cells, improving the energy balance and functions of the insulin. As a feed additive, chromium(III) pyridine-2-carboxylate can not only increase the proportion of lean meat, reduce fat content and improve the carcass quality, but also enhance the animals' anti-stress ability and immunity, thereby promoting the yield of animal products. In August 2005, the US Food and Drug Administration (FDA) approved the production of chromium(III) pyridine-2-carboxylate, and confirmed that it is safe to apply chromium(III) pyridine-2-carboxylate in the treatment of insulin resistance type II diabetes.
There are four primary methods of preparing chromium(III) pyridine-2-carboxylate. In method 1, pyridine-2-carboxylic acid is reacted with potassium hydroxide in ethanol to form potassium pyridine-2-carboxylate which is then reacted with chromium trichloride dissolved in ethanol to produce chromium(III) pyridine-2-carboxylate. In method 2, pyridine-2-carboxylic acid is reacted with sodium hydroxide in water to form sodium pyridine-2-carboxylate which is then reacted with chromium(III) nitrate to produce chromium(III) pyridine-2-carboxylate. In method 3, 2-methylpyridine is oxidized by chromic anhydride into pyridine-2-carboxylic acid in the presence of sulfuric acid and then the pyridine-2-carboxylic acid is complexed with trivalent chromium under acidic conditions to produce chromium(III) pyridine-2-carboxylate, where the excessive chromic anhydride is removed by ethanol reduction and the excess trivalent chromium is removed by alkalization. The key step in this method is to oxidize the methyl in the 2-methylpyridine into a carboxyl group. In method 4, 2-methylpyridine is oxidized by potassium permanganate into pyridine-2-carboxylic acid followed by filtration to remove MnO2 and complexation to produce chromium(III) pyridine-2-carboxylate.
The application discloses a method of preparing chromium(III) pyridine-2-carboxylate using 2-OP rectification residues, which relates to a cleaner production technology in the high-value utilization and reduction of chemical hazardous solid wastes.
In order to develop a method of preparing chromium(III) pyridine-2-carboxylate using 2-OP rectification residues, the references are made to many publications related to the preparation, application and analysis of pyridine-2-carbonitrile, pyridine-2-carboxylic acid and chromium(III) pyridine-2-carboxylate; for example, Transition metal-free synthesis of primary amides from aldehydes and hydroxylamine hydrochloride, Tetrahedron Letters, 2014, Vol. 55, No. 20; Progress in preparation of pyridinecarboxylic acids, Chemical Research and Applications, 2003, Vol. 15, No. 2; Synthesis of 3,6-dichloropicolinic acid, CIESC Journal, 2011, Vol. 62, No. 9; Electrochemical synthesis of 3,6-dichloropicolinic acid and its industrialization, CIESC Journal, 2010, Vol. 61, No. 3; Synthesis and characterization of cobalt(II) and nickel(II) complexes of 2-picolinic acid by room temperature solid-solid reaction, Fine Chemicals, 2013, Vol. 30, No. 3; Synthesis and application of nicotinic acid, Applied Chemical Industry, 2010, Vol. 39, No. 10; Study on V—Ti—O—Mo catalysts for 2-cyanopyridine synthesis via gas-solid ammoxidation, Journal of Chemical Engineering of Chinese Universities, 2016, Vol. 30, No. 4; Improvement on the technologic process of synthesis of 2-pyridinecarboxylic acid, Hubei Chemical Industry, 2001, Vol. 18, No. 2; Synthesis of 2-pyridinecarboxylic acid by oxidation with KMnO4, Chemical Research, 2010, Vol. 21, No. 1; Synthesis of 2-pyridinecarboxylic acid oxidation of potassium dichromate, Journal of Molecular Science, 2007, Vol. 23, No. 2; Technology improvement of chromium 2-picolinate, Hebei Journal of Industrial Science & Technology, 2015, Vol. 32, No. 6; Improved synthesis of chromium 2-picolinate, Feed Industry, 2001, Vol. 22, No. 5; Synthesis and biological activity of chromium pyridine carboxylates, Chemical Reagents, 2001, Vol. 23, No. 6; A new process of synthesis of chromium-2-picolinate by chromic anhydride oxidation, Chemical Engineer, 2005, No. 9; Ammonia oxidation catalytic synthesis of 2-cyanopyrazine, Journal of Chemistry and Chemical Engineering, 2005, Vol. 19, No. 6; Ammoxidation of 2-picoline catalyzed by modified V2O5/TiO2, Monatshefte für chemie-chemical monthly, 2014, Vol. 145, No. 8; Study on the technologic process of synthesis of chromium 2-picolinate, Chemical Engineer, 2004, No. 1; The preparation of isonicotinic and picolinic acids, Journal of American Chemistry Society, 1952, Vol. 74, No. 21; Studies on the conditions of synthesis of picolinic acid by heterogeneous catalytic oxidation of 2-picoline, Catalysis Letters, 1998, Vol. 54, No. 1; and Feed additive chromium picolinate, Chinese NY Industry Standard, NY/T 916-2004.